The ideal therapy for lupus nephritis (LN) should reduce mortality. Although cyclophosphamide (CYC) has been used in the clinical setting for 30 years, the ability of this drug to achieve this goal is not supported by robust evidence.
The first National Institutes for Health (NIH) trial in 1986 led to a shift from oral to intravenous (IV) CYC. The three NIH trials together then led to the dogma that high-dose IV CYC is the only cytotoxic agent superior to steroids alone in LN and to its general acceptance as the standard of care. Since then, high-dose IV CYC has been shown to have no impact on survival and to have a large number of adverse effects.
The Euro-Lupus Nephritis Trial found that low-dose IV CYC could be used as an alternative to high-dose regimens and was associated with fewer secondary effects. Other studies have shown that other agents such as mycophenolate mofetil (MMF) have similar or even greater efficacy and a better safety profile.
IV CYC is the only drug for which long-term data on LN is available. As evidence of other therapies such as MMF accumulates, however, IV CYC might no longer be considered the standard treatment for LN.
